DOCSLIB.ORG

Differential Expression of the CCN Family Members Cyr61, CTGF and Nov in Human Breast Cancer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Differential Expression of the CCN Family Members Cyr61, CTGF and Nov in Human Breast Cancer Endocrine-Related Cancer (2004) 11 781–791 Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer Wen G Jiang, Gareth Watkins, Oystein Fodstad 1, Anthony Douglas-Jones 2, Kefah Mokbel 3 and Robert E Mansel Metastasis & Angiogenesis Research Group, University of Wales College of Medicine, Cardiff University, Cardiff, UK 1Cancer Research Institute, University of South Alabama, Mobile, AL, USA 2Pathology, University of Wales College of Medicine, Cardiff University, Cardiff, UK 3Department of Surgery, St George Hospital, London, UK (Requests for offprints should be addressed to W G Jiang; Email: [email protected]) Abstract The CCN family members cysteine-rich 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/ CCN2) and nephroblastoma over-expressed (Nov/CCN3) play diverse roles in cells, are known to regulate cell growth, adhesion, matrix production and migration and are involved in endocrine- regulated pathways in various cell types. The role of these molecules in cancer remains controversial. In a cohort of 122 human breast tumours (together with 32 normal breast tissues) we have analysed the expression of all three CCN members at the mRNA and protein levels. Significantly higher levels of Cyr61 ðP ¼ 0:02Þ, but low levels of CTGF and Nov, were seen in tumour tissues compared with normal tissues. Significantly raised levels of Cyr61 were associated with poor prognosis ðP ¼ 0:02Þ, nodal involvement ðP ¼ 0:03Þ and metastatic disease ðP ¼ 0:016Þ. Patients who died of breast cancer also had high levels of Cyr61. In contrast, CTGF in patients with poor prognosis ðP ¼ 0:021Þ, metastasis ðP ¼ 0:012Þ, local recurrence ðP ¼ 0:0024Þ and mortality ðP ¼ 0:0072Þ had markedly reduced levels. Similar to CTGF, low levels of Nov were also seen in patients with poor prognosis and mortality and with significantly decreased survival (P ¼ 0:033 and P ¼ 0:0146, respectively). This result was fully supported by immunohistochemical analysis of frozen sectioned tissues. While fibroblasts and endothelial cells generally expressed good levels of all three CCN proteins, highly invasive MDA MB 231 cells expressed lower levels of CTGF and Nov, but higher levels of Cyr61, than the less invasive MCF-7. It is concluded that members of the CCN family are differentially expressed and may play important but contrasting roles in the progressive nature of human breast cancer. While Cyr61 appears to act as a factor stimulating aggressiveness, CTGF and Nov may act as tumour suppressors. Endocrine-Related Cancer (2004) 11 781–791 Introduction activities probably occur through the ability of CCN proteins to bind and activate cell-surface integrins and The CCN family comprises cysteine-rich 61 (Cyr61/ intracellular signalling molecules including fibulin 1C, CCN1), connective tissue growth factor (CTGF/CCN2) Notch 1, S100A4 and ion channels (Perbel 2004). and nephroblastoma over-expressed (Nov/CCN3). Accumulating evidence supports a role for these factors Recently the Wnt-induced secreted proteins (WISPs) in endocrine pathways and endocrine-related processes. have been found to also belong to the CCN family and Despite the progress in understanding the biology of these so WISP-1 has been named CCN4, WISP-2 is CCN5 and molecules in cells and signalling pathways, the role of the WISP-3 is CCN6. These proteins stimulate mitosis, CCN members in cancer is far from clear and the results adhesion, apoptosis, extracellular matrix production, in the literature remain controversial. growth arrest and migration of multiple cell types (for a Cyr61 is a known angiogenic factor (Babic et al. 1998, recent review, see Brigstock 2003). Many of these Mo et al. 2002), which acts probably by regulating pro- Endocrine-Related Cancer (2004) 11 781–791 DOI:10.1677/erc.1.00825 1351-0088/04/011–781 # 2004 Society for Endocrinology Printed in Great Britain Online version via http://www.endocrinology-journals.org Downloaded from Bioscientifica.com at 09/24/2021 02:32:55PM via free access Jiang et al.: CCN family in human breast cancer Table 1 Clinical information on patients in the study exhibited lower levels in breast tumours and were inversely linked to a poor prognosis, suggesting that differentially Clinical Information n expressed CCN members may have clear contrasting roles Nodal status Negative 65 in the development of human breast cancer. Positive 55 Grade Grade 1 23 Materials and methods Grade 2 41 Grade 3 56 Sample collection TNM staging TNM-1 69 TNM-2 60 Human breast cancer cell lines MCF-7 and MDA MB TNM-3 7 231, and human fibroblast cell line MRC-5, were TNM-4 4 purchased from the European Collection of Animal Cell Clinical outcome Disease-free 87 Cultures (ECACC, Salisbury, Hants, UK). Human With metastasis 6 umbilical vein endothelial cells (HUVECs) were pur- With local recurrence 5 chased from TCS Biologicals (Oxford, UK). Breast cancer Died of breast cancer 19 tissues ðn ¼ 120Þ and normal background tissues ðn ¼ 32Þ were collected immediately after surgery and stored in a angiogenic integrins (Tsai et al. 2000, Leu et al. 2002). deep freeze until use. Patients were routinely followed MCF-7 breast cancer cells, when transfected with Cyr61, clinically after surgery. The median follow-up period was acquire hormone independence and anti-oestrogen resis- 72 months for the current study. The presence of tumour tance. These cells become tumorigenic and invasive, cells in the collected tissues was verified by a consultant accompanied by increased angiogenic activities. Cyr61 pathologist (A D-J), who examined Hematoxylin and has been indicated in tumorigenesis and disease progres- Eosin (H&E)-stained frozen sections. Details of the sion in breast tumour models (Tasi et al. 2002a). Cyr61 histology were obtained from pathology reports and expression can be up-regulated by hormones such as have been given in Table 1. progestin (Sampath et al. 2002), and agents including Materials phorbol ester and vitamins D and E2 (Sampeth et al. 2001, Tsai et al. 2002b), but down-regulated by retinoic acid (Tsai RNA-extraction kit and RT kit were obtained from et al. 2002b). The role for CTGF/CCN2 in cancer is far less AbGene, Guildford, Surrey, UK. PCR primers were clear. CTGF has been shown to affect cell-cycle progres- designed using Beacon Designer (Palo Alto, CA, USA) sion, by up-regulating cyclin A and reducing p27kip1 and synthesized by Invitrogen (Paisley, Scotland, UK). (Kothapalli and Grotendorst 2000). CTGF has been Molecular-biology-grade agarose and DNA ladder were found to be highly expressed in proliferating endothelial from Invitrogen. Mastermix for routine PCR and cells and glioma cells (Pan et al. 2002). In breast cancer quantitative PCR was from AbGene. Goat anti-human cells, CTGF mRNA was found to be absent from MCF-7. Cyr61, CTGF and Nov antibodies were purchased from Transfection of MCF-7 with CTGF expression vector Santa Cruz Biotechnology (Santa Cruz, CA, USA). results in a high degree of apoptosis (Hishikawa et al. Tissue processing, RNA extraction and cDNA 1999). This has been supported partly by a recent study synthesis which shows that over-expression of CTGF in oral squamous cell carcinoma results in reduction in cell growth Frozen sections of tissues were cut at a thickness of 5– and tumorigenesis (Moritani et al. 2003). Nov/CCN3 is 10 mm and kept for immunohistochemistry and routine probably the least-studied CCN member. Nov has been histology (Jiang et al. 2003a). A further 15–20 sections indicated to stimulate the proliferation of fibroblasts (Liu were homogenized using a hand-held homogenizer in ice- et al. 1999). Over-expression of Nov in glioma cells results cold RNA extraction solution. The concentration of RNA in cells with slower growth rate and low tumorigenicity was determined using a UV spectrophotometer. Reverse (Gupta et al. 2001). transcription was carried out using an RT kit with an Thus, the role of the CCN family in clinical cancer is anchored oligo-dT primer supplied by AbGene, using 1 mg unclear and in many cases remains controversial. In the total RNA in a 96-well plate. The quality of cDNA was current study, we have examined the relationship between verified using b-actin primers. Cyr61, CTGF and Nov at the mRNA and protein levels in a cohort of human breast cancer, and studied the clinical Quantitative analysis of CCN family members outcomes. We report here that while Cyr61 was highly over-expressed in tumour tissues and was linked to the The transcript level of the CCN family members from the progressive nature of breast tumours, CTGF and Nov above-prepared cDNA was determined using a real-time 782 www.endocrinology-journals.org Downloaded from Bioscientifica.com at 09/24/2021 02:32:55PM via free access Endocrine-Related Cancer (2004) 11 781–791 quantitative PCR, based on the AmplifluorTM technology al. 2003c). The sections were mounted on Super Frost (Nazarenko et al. 1997), modified from a previously Plus microscope slides, air dried and then fixed in a reported method (Jiang et al. 2003a, 2003b). Briefly, a mixture of 50% acetone/50% methanol. The sections pair of PCR primers was designed using the Beacon were then placed in Optimax wash buffer for 5–10 min to Designer software (version 2). To one of the primers rehydrate. Sections were incubated for 20 min in a 0.6% (routinely the antisense primer in our laboratory), an BSA blocking solution and probed with the primary additional sequence, known as the Z sequence (50- antibody. Following extensive washings, sections were ACTGAACCTGACCGTACA-30), which is complemen- incubated for 30 min with the secondary biotinylated tary to the universal Z probe (Nazarenko et al. 1997; antibody (Multilink Swine anti-goat/mouse/rabbit immu- Intergen, Oxford, UK), was added. A Taqman detection noglobulin; Dako, Ely, Cambs, UK). Following wash- kit for b-actin was purchased from Perkin-Elmer.
Load more

Recommended publications
  • Genetic Analysis of the Roles of Hh, FGF8, and Nodal Signaling During Catecholaminergic System Development in the Zebrafish Brain
    The Journal of Neuroscience, July 2, 2003 • 23(13):5507–5519 • 5507 Development/Plasticity/Repair Genetic Analysis of the Roles of Hh, FGF8, and Nodal Signaling during Catecholaminergic System Development in the Zebrafish Brain Jochen Holzschuh, Giselbert Hauptmann, and Wolfgang Driever Developmental Biology, Institute Biology 1, University of Freiburg, D-79104 Freiburg, Germany CNS catecholaminergic neurons can be distinguished by their neurotransmitters as dopaminergic or noradrenergic and form in distinct regions at characteristic embryonic stages. This raises the question of whether all catecholaminergic neurons of one transmitter type are specified by the same set of factors. Therefore, we performed genetic analyses to define signaling requirements for the specification of distinct clusters of catecholaminergic neurons in zebrafish. In mutants affecting midbrain–hindbrain boundary (MHB) organizer for- mation, the earliest ventral diencephalic dopaminergic neurons appear normal. However, after2dofdevelopment, we observed fewer cells than in wild types, which suggests that the MHB provides proliferation or survival factors rather than specifying ventral diencephalic dopaminergic clusters. In hedgehog (Hh) pathway mutants, the formation of catecholaminergic neurons is affected only in the pretectal cluster. Surprisingly, neither fibroblast growth factor 8 (FGF8) alone nor in combination with Hh signaling is required for specification of early developing dopaminergic neurons. We analyzed the formation of prosomeric territories in the forebrain of Hh and Nodal pathway mutants to determine whether the absence of specific dopaminergic clusters may be caused by early patterning defects ablating corre- sponding parts of the CNS. In Nodal pathway mutants, ventral diencephalic and pretectal catecholaminergic neurons fail to develop, whereas both anatomical structures form at least in part.
    [Show full text]
  • Epha Receptors and Ephrin-A Ligands Are Upregulated by Monocytic
    Mukai et al. BMC Cell Biology (2017) 18:28 DOI 10.1186/s12860-017-0144-x RESEARCHARTICLE Open Access EphA receptors and ephrin-A ligands are upregulated by monocytic differentiation/ maturation and promote cell adhesion and protrusion formation in HL60 monocytes Midori Mukai, Norihiko Suruga, Noritaka Saeki and Kazushige Ogawa* Abstract Background: Eph signaling is known to induce contrasting cell behaviors such as promoting and inhibiting cell adhesion/ spreading by altering F-actin organization and influencing integrin activities. We have previously demonstrated that EphA2 stimulation by ephrin-A1 promotes cell adhesion through interaction with integrins and integrin ligands in two monocyte/ macrophage cell lines. Although mature mononuclear leukocytes express several members of the EphA/ephrin-A subclass, their expression has not been examined in monocytes undergoing during differentiation and maturation. Results: Using RT-PCR, we have shown that EphA2, ephrin-A1, and ephrin-A2 expression was upregulated in murine bone marrow mononuclear cells during monocyte maturation. Moreover, EphA2 and EphA4 expression was induced, and ephrin-A4 expression was upregulated, in a human promyelocytic leukemia cell line, HL60, along with monocyte differentiation toward the classical CD14++CD16− monocyte subset. Using RT-PCR and flow cytometry, we have also shown that expression levels of αL, αM, αX, and β2 integrin subunits were upregulated in HL60 cells along with monocyte differentiation while those of α4, α5, α6, and β1 subunits were unchanged. Using a cell attachment stripe assay, we have shown that stimulation by EphA as well as ephrin-A, likely promoted adhesion to an integrin ligand- coated surface in HL60 monocytes. Moreover, EphA and ephrin-A stimulation likely promoted the formation of protrusions in HL60 monocytes.
    [Show full text]
  • Ephb3 Suppresses Non-Small-Cell Lung Cancer Metastasis Via a PP2A/RACK1/Akt Signalling Complex
    ARTICLE Received 7 Nov 2011 | Accepted 11 Jan 2012 | Published 7 Feb 2012 DOI: 10.1038/ncomms1675 EphB3 suppresses non-small-cell lung cancer metastasis via a PP2A/RACK1/Akt signalling complex Guo Li1, Xiao-Dan Ji1, Hong Gao1, Jiang-Sha Zhao1, Jun-Feng Xu1, Zhi-Jian Sun1, Yue-Zhen Deng1, Shuo Shi1, Yu-Xiong Feng1, Yin-Qiu Zhu1, Tao Wang2, Jing-Jing Li1 & Dong Xie1 Eph receptors are implicated in regulating the malignant progression of cancer. Here we find that despite overexpression of EphB3 in human non-small-cell lung cancer, as reported previously, the expression of its cognate ligands, either ephrin-B1 or ephrin-B2, is significantly downregulated, leading to reduced tyrosine phosphorylation of EphB3. Forced activation of EphB3 kinase in EphB3-overexpressing non-small-cell lung cancer cells inhibits cell migratory capability in vitro as well as metastatic seeding in vivo. Furthermore, we identify a novel EphB3-binding protein, the receptor for activated C-kinase 1, which mediates the assembly of a ternary signal complex comprising protein phosphatase 2A, Akt and itself in response to EphB3 activation, leading to reduced Akt phosphorylation and subsequent inhibition of cell migration. Our study reveals a novel tumour-suppressive signalling pathway associated with kinase-activated EphB3 in non-small-cell lung cancer, and provides a potential therapeutic strategy by activating EphB3 signalling, thus inhibiting tumour metastasis. 1 Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of Chinese Academy of Sciences, Shanghai 200031, China. 2 The Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai 200433, China.
    [Show full text]
  • Fgf8b Oncogene Mediates Proliferation and Invasion of Epstein–Barr Virus-Associated Nasopharyngeal Carcinoma Cells: Implication for Viral-Mediated Fgf8b Upregulation
    Oncogene (2011) 30, 1518–1530 & 2011 Macmillan Publishers Limited All rights reserved 0950-9232/11 www.nature.com/onc ORIGINAL ARTICLE FGF8b oncogene mediates proliferation and invasion of Epstein–Barr virus-associated nasopharyngeal carcinoma cells: implication for viral-mediated FGF8b upregulation VWY Lui1,7, DM-S Yau1,7, CS-F Cheung1, SCC Wong1, AK-C Chan2, Q Zhou1, EY-L Wong1, CPY Lau1, EKY Lam1, EP Hui1, B Hong1, CWC Hui1, AS-K Chan1, PKS Ng3, Y-K Ng4, K-W Lo5, CM Tsang6, SKW Tsui3, S-W Tsao6 and ATC Chan1 1State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong; 2Department of Pathology, Queen Elizabeth Hospital, Hong Kong; 3School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong; 4Department of Surgery, Chinese University of Hong Kong, Hong Kong; 5Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong and 6Department of Anatomy, University of Hong Kong, Hong Kong The fibroblast growth factor 8b (FGF8b) oncogene is identified LMP1 as the first viral oncogene capable of known to be primarily involved in the tumorigenesis and directly inducing FGF8b (an important cellular oncogene) progression of hormone-related cancers. Its role in other expression in human cancer cells. This novel mechanism of epithelial cancers has not been investigated, except for viral-mediated FGF8 upregulation may implicate a new esophageal cancer, in which FGF8b overexpression was role of oncoviruses in human carcinogenesis. mainly found in tumor biopsies of male patients. These Oncogene (2011) 30, 1518–1530; doi:10.1038/onc.2010.529; observations were consistent with previous findings in published online 29 November 2010 these cancer types that the male sex-hormone androgen is responsible for FGF8b expression.
    [Show full text]
  • Hepatocyte Growth Factor Signaling Pathway As a Potential Target in Ductal Adenocarcinoma of the Pancreas
    JOP. J Pancreas (Online) 2017 Nov 30; 18(6):448-457. REVIEW ARTICLE Hepatocyte Growth Factor Signaling Pathway as a Potential Target in Ductal Adenocarcinoma of the Pancreas Samra Gafarli, Ming Tian, Felix Rückert Department of Surgery, Medical Faculty Mannheim, University of Heidelberg, Germany ABSTRACT Hepatocyte growth factor is an important cellular signal pathway. The pathway regulates mitogenesis, morphogenesis, cell migration, invasiveness and survival. Hepatocyte growth factor acts through activation of tyrosine kinase receptor c-Met (mesenchymal epithelial transition factor) as the only known ligand. Despite the fact that hepatocyte growth factor is secreted only by mesenchymal origin cells, the targets of this multifunctional pathway are cells of mesenchymal as well as epithelial origin. Besides its physiological role recent evidences suggest that HGF/c-Met also plays a role in tumor pathophysiology. As a “scatter factor” hepatocyte growth factor stimulates cancer cell migration, invasion and subsequently promote metastases. Hepatocyte growth factor further is involved in desmoplastic reaction and consequently indorse chemo- and radiotherapy resistance. Explicitly, this pathway seems to mediate cancer cell aggressiveness and to correlate with poor prognosis and survival rate. Pancreatic Ductal Adenocarcinoma is a carcinoma with high aggressiveness and metastases rate. Latest insights show that the HGF/c-Met signal pathway might play an important role in pancreatic ductal adenocarcinoma pathophysiology. In the present review, we highlight the role of HGF/c-Met pathway in pancreatic ductal adenocarcinoma with focus on its effect on cellular pathophysiology and discuss its role as a potential therapeutic target in pancreatic ductal adenocarcinoma. INTRODUCTION activation causes auto-phosphorylation of c-Met and subsequent activation of downstream signaling pathways Hepatocyte growth factor (HGF) is a multifunctional such as mitogen-activated protein kinases (MAPKs), gene.
    [Show full text]
  • Involvement of Cyr61 in the Growth, Invasiveness and Adhesion of Esophageal Squamous Cell Carcinoma Cells
    INTERNATIONAL JOURNAL OF MoleCular MEDICine 27: 429-434, 2011 Involvement of Cyr61 in the growth, invasiveness and adhesion of esophageal squamous cell carcinoma cells JIAN-JUN XIE1, LI-YAN XU2, YANG-MIN XIE3, ZE-PENG DU2, CAI-HUA FENG1, HUI-DONG1 and EN-MIN LI1 1Department of Biochemistry and Molecular Biology, 2Institute of Oncologic Pathology, The Key Immunopathology Laboratory of Guangdong Province and 3Department of Experimental Animal Center, Medical College of Shantou University, Shantou 515041, P.R. China Received October 27, 2010; Accepted December 29, 2010 DOI: 10.3892/ijmm.2011.603 Abstract. Cysteine-rich 61 (Cyr61), a secreted protein which overexpressed (Nov/CCN3), Wnt-1 induced secreted protein 1 belongs to the CCN family, has been found to be differentially (Wisp-1/CCN4), Wisp-2/CCN5, and Wisp-3/CCN6 (1,2). expressed in many cancers and to be involved in tumor Encoded by a growth factor-inducible immediate early gene, progression. The expression of Cyr61 in esophageal squamous Cyr61 is a 40 kDa protein which is extremely cysteine-rich. cell carcinoma (ESCC) has only recently been described, but This heparin-binding protein shares a 40-50% amino acid the roles of Cyr61 in ESCC cells still remained unclear. In homology with the other CCN family members. An important this study, we have shown that there are high levels of Cyr61 structural feature of CCN proteins is that they contain four in ESCC cell lines. Furthermore, using RNA interference conserved modules which exhibit similarities to the insulin-like (RNAi), we stably silenced the expression of Cyr61 in EC109 growth factor-binding proteins (IGFBPs), the von Willebrand cells, an ESCC cell line.
    [Show full text]
  • Investigations of Ephrin Ligands During Development
    lB-c'è-C,-a Investigations of ephrin ligands during development A thesis submitted for the degree of Doctor of Philosophy Molecular Biosciences, Adelaide University By Paul Tosch, B.Sc (Hons.) Department of Molecular Bioscience, Adelaide University, Australia, Adelaide, South Australia, 5005 CNUcE L IÙ'day 2002 2 4 I think and think for months and years. Ninety-nine times, the conclusion is false. The hundredth time I am right. Albert Einstein (1879-1955), German-born U.S. theoretical physicist. 5 6 Acknowledgments Well what an amazing experience my PhD has been, I am not sure if I have grown more as a person or more as an academic. It is obvious that I could not have achieved any of this without the contributions of a large number of people. I would like to thank the following people: Paul Moir for driving me across the desert and giving me somewhere to live, he is like the brother I never had (it's getting a bit sand duney around here hey). Jacinta Makin for putting up with and listening to countless theories, and teaching me to ride horses. My two supervisors Dr Simon Koblar and Dr Robert Saint for providing me with the resources to perform this work. The following postdocs for providing challenging my mind and pushing me beyond my limits: Dr Tetyana Shandala, Dr Daniel Kortschak, Dr Rory Hope, Dr Tim Cox' The members of the Koblar lab past and present: Agnes Stokowski, Edwina Ashby, Chathurani Jayesena (Chaza), Anthony Condina, Dr Warren Flood (Wazza), Dr Robert Moyer , and Rebecca Mclennon The members of the Hope lab: Dave Wheeler, Scott Spargo The members of the Saint lab: Julianne Camerotto, Volkan Evci, Greg Somers (Gregor), Peter Smibert, Donna Crack, Jane Sibbons, Michelle Coulson, Member of the genetics department: Velta Vingelis, Itty Bitty Kitty People who have helped out at various times: Rebecca Patrick, Vera Shandala, Ian Miller, Calluna Denwood, James Brooks, Matthew Kelcey, Dr Peter Gunn, and Martin Blanchard.
    [Show full text]
  • Differential Expression of the CCN Family Members Cyr61, CTGF and Nov in Human Breast Cancer
    Endocrine-Related Cancer (2004) 11 781–791 Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer Wen G Jiang, Gareth Watkins, Oystein Fodstad 1, Anthony Douglas-Jones 2, Kefah Mokbel 3 and Robert E Mansel Metastasis & Angiogenesis Research Group, University of Wales College of Medicine, Cardiff University, Cardiff, UK 1Cancer Research Institute, University of South Alabama, Mobile, AL, USA 2Pathology, University of Wales College of Medicine, Cardiff University, Cardiff, UK 3Department of Surgery, St George Hospital, London, UK (Requests for offprints should be addressed to W G Jiang; Email: [email protected]) Abstract The CCN family members cysteine-rich 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/ CCN2) and nephroblastoma over-expressed (Nov/CCN3) play diverse roles in cells, are known to regulate cell growth, adhesion, matrix production and migration and are involved in endocrine- regulated pathways in various cell types. The role of these molecules in cancer remains controversial. In a cohort of 122 human breast tumours (together with 32 normal breast tissues) we have analysed the expression of all three CCN members at the mRNA and protein levels. Significantly higher levels of Cyr61 ðP ¼ 0:02Þ, but low levels of CTGF and Nov, were seen in tumour tissues compared with normal tissues. Significantly raised levels of Cyr61 were associated with poor prognosis ðP ¼ 0:02Þ, nodal involvement ðP ¼ 0:03Þ and metastatic disease ðP ¼ 0:016Þ. Patients who died of breast cancer also had high levels of Cyr61. In contrast, CTGF in patients with poor prognosis ðP ¼ 0:021Þ, metastasis ðP ¼ 0:012Þ, local recurrence ðP ¼ 0:0024Þ and mortality ðP ¼ 0:0072Þ had markedly reduced levels.
    [Show full text]
  • Metabolic and Mitogenic Functions of FGF1
    University of Groningen Metabolic and mitogenic functions of fibroblast growth factor 1 Struik, Dicky DOI: 10.33612/diss.133879075 IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2020 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Struik, D. (2020). Metabolic and mitogenic functions of fibroblast growth factor 1. University of Groningen. https://doi.org/10.33612/diss.133879075 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 25-09-2021 Chapter 2 : Fibroblast Growth Factors in control of lipid metabolism: from biological function to clinical application Dicky Struik , Marleen B. Dommerholt and Johan W. Jonker Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Current Opinion in Lipidology, 2019, 30(3), 235-243.
    [Show full text]
  • Gene Section Review
    Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL INIST-CNRS Gene Section Review EPHA3 (EPH receptor A3) Peter W. Janes Department of Biochemistry, Molecular Biology, Monash University, Wellington Road, Clayton, VIC, 3800, Australia. [email protected] Published in Atlas Database: July 2015 Online updated version : http://AtlasGeneticsOncology.org/Genes/EPHA3ID40463ch3p11.html Printable original version : http://documents.irevues.inist.fr/bitstream/handle/2042/62775/07-2015-EPHA3ID40463ch3p11.pdf DOI: 10.4267/2042/62775 This article is an update of : Stringer B, Day B, McCarron J, Lackmann M, Boyd A. EPHA3 (EPH receptor A3). Atlas Genet Cytogenet Oncol Haematol 2010;14(3) This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2016 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Local order (tel) C3orf38 (ENSG00000179021) ->, 949,562bp, HGNC (Hugo): EPHA3 EPHA3 (374,609bp) ->, 720,071bp, <- Location: 3p11.1 AC139337.5 (ENSG00000189002) (cen) Other names: EC 2.7.10.1, ETK, ETK1, EphA3, Note HEK, HEK4, TYRO4 EPHA3 is flanked by two gene deserts. Figure 1: Chromosomal location of EPHA3 (based on Ensembl Homo sapiens version 53.36o (NCBI36)). Figure 2: Genomic neighbourhood of EPHA3 (based on Ensembl Homo sapiens version 53.36o (NCBI36)). Figure 3: Genomic organisation of EPHA3. Atlas Genet Cytogenet Oncol Haematol. 2016; 20(5) 264 EPHA3 (EPH receptor A3) Janes PW Figure 4: Domain organisation of EphA3. molecular mass of the translated protein minus the DNA/RNA signal peptide is 92.8kDa. The 521 amino acid Note extracellular domain contains five potential sites for EPHA3 spans the human tile path clones CTD- N-glycosylation such that EphA3 is typically 2532M17, RP11-784B9 and RP11-547K2.
    [Show full text]
  • Hypercalcemia of Malignancy: an Update on Pathogenesis and Management Aibek E
    University of Kentucky UKnowledge Internal Medicine Faculty Publications Internal Medicine 11-2015 Hypercalcemia of Malignancy: An Update on Pathogenesis and Management Aibek E. Mirrakhimov University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits oy u. Follow this and additional works at: https://uknowledge.uky.edu/internalmedicine_facpub Part of the Medicine and Health Sciences Commons Repository Citation Mirrakhimov, Aibek E., "Hypercalcemia of Malignancy: An Update on Pathogenesis and Management" (2015). Internal Medicine Faculty Publications. 82. https://uknowledge.uky.edu/internalmedicine_facpub/82 This Article is brought to you for free and open access by the Internal Medicine at UKnowledge. It has been accepted for inclusion in Internal Medicine Faculty Publications by an authorized administrator of UKnowledge. For more information, please contact [email protected]. Hypercalcemia of Malignancy: An Update on Pathogenesis and Management Notes/Citation Information Published in North American Journal of Medical Sciences, v. 7, no. 11, p. 483-493. © 2015 North American Journal of Medical Sciences | Published by Wolters Kluwer - Medknow This is an open access article distributed under the terms of the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non- commercially, as long as the author is credited and the new creations are licensed under the identical terms. Digital Object Identifier (DOI) http://dx.doi.org/10.4103/1947-2714.170600 This article is available at UKnowledge: https://uknowledge.uky.edu/internalmedicine_facpub/82 [Downloaded free from http://www.najms.org on Friday, November 27, 2015, IP: 202.164.43.126] Review Article Hypercalcemia of Malignancy: An Update on Pathogenesis and Management Aibek E.
    [Show full text]
  • Hypercalcemia of Malignancy: an Update on Pathogenesis and Management
    [Downloaded free from http://www.najms.org on Thursday, July 16, 2020, IP: 69.27.229.130] Review Article Hypercalcemia of Malignancy: An Update on Pathogenesis and Management Aibek E. Mirrakhimov Department of Medicine, University of Kentucky School of Medicine, 800 Rose Street, Lexington, KY 40536, USA Abstract Hypercalcemia of malignancy is a common finding typically found in patients with advanced stage cancers. We aimed to provide an updated review on the etiology, pathogenesis, clinical presentation, and management of malignancy-related hypercalcemia. We searched PubMed/Medline, Scopus, Embase, and Web of Science for original articles, case reports, and case series articles focused on hypercalcemia of malignancy published from 1950 to December 2014. Hypercalcemia of malignancy usually presents with markedly elevated calcium levels and therefore, usually severely symptomatic. Several major mechanisms are responsible for the development of hypercalcemia of malignancy including parathyroid hormone-related peptide-mediated humoral hypercalcemia, osteolytic metastases-related hypercalcemia, 1,25 Vitamin D-mediated hypercalcemia, and parathyroid hormone-mediated hypercalcemia in patients with parathyroid carcinoma and extra parathyroid cancers. Diagnosis should include the history and physical examination as well as measurement of the above mediators of hypercalcemia. Management includes hydration, calcitonin, bisphosphonates, denosumab, and in certain patients, prednisone and cinacalcet. Patients with advanced underlying kidney disease and refractory severe hypercalcemia should be considered for hemodialysis. Hematology or oncology and palliative care specialists should be involved early to guide the options of cancer targeted therapies and help the patients and their closed ones with the discussion of comfort-oriented care. Keywords: Cancer, hypercalcemia, parathyroid hormone related peptide, vitamin D Address for correspondence: Dr.
    [Show full text]